The MHC class II transactivator (CIITA), a master regulator of many MHC locus genes, functions as a transcriptional coactivator, associating with DNA binding proteins that influence promoter accessibility and transcription initiation. Unlike constitutively expressed transcription factors such as RFX, NF-Y and CREB, that bind MHC class II locus promoters, CIITA expression is cytokine-inducible and regulated by cell type and differentiation stage. Thus, CIITA expression in dendritic cells regulates surface levels of MHC class II receptors in response to environmental stimuli influencing the maturation state of these cells. CIITA also regulates the expression of non-MHC genes. Dendritic cells from mice deficient in CIITA do not express the semaphorin receptor, Plexin-A1 (PlexA1). PlexA1 expression regulates interactions between dendritic cells and T lymphocytes. Interestingly, PlexA1 expression is developmentally regulated in dendritic cells, perhaps through interactions of the promoter with CIITA. However, the mechanisms of CIITA regulation of PlexA1 expression have yet to be examined. The goal of this proposal is to elucidate the molecular regulation of PlexA1 expression by CIITA and the associating transcription factors in dendritic cells.